Single-cell eQTL mapping in PBMCs reveals genes that modulate the immune response in atherosclerosis 3202

Description Atherosclerosis is a chronic inflammatory disease of large arteries and is the underlying pathological process behind cardiovascular disease (CVD). The heritability of CVD is estimated to be between 30-60%. However, most of the genetic risk loci for CVD identified by genome-wide association studies have unknown functions. In this study, we are conducting quantitative trait loci (QTL) analysis of peripheral blood mononuclear cells (PBMCs) using genotyping and CITE-seq data from subclinical CVD patients in the women’s interagency HIV study (WIHS). This analysis identifies which of our 2.2 million single nucleotide polymorphisms (SNPs) is significantly associated with a change in mRNA level of a protein-coding gene within 1 MB of the SNP (known as cis-eQTLs). We have found several significant single-cell eQTLs that are novel. Most are specific for just one immune cell type. We found a set of SNPs impacting expression for interferon-γ receptor 1 (IFNGR1) in CD4+ T cells. There are also two SNPs that impact IFN-γ expression in CD8+ T cells, one of the primary sources of this cytokine. We are now testing how the protein levels of IFNGR1/IFN-γ are impacted. This serves as just one example of the significant results from this study that reveal how genetics influence CVD through immune cells. Funding Sources Supported by NIH 5R01HL148094-02; NIH 5R35HL145241-07. Topic Categories Computational and Systems Immunology (COMP)